The obesity epidemic in 32,936 youth with type 1 diabetes (T1D) in the German/Austrian DPV and US T1D Exchange (T1DX) registries

Objective To examine the current extent of the obesity problem in 2 large pediatric clinical registries in the US and Europe and to examine the hypotheses that increased body mass index (BMI) z-scores (BMIz) are associated with greater hemoglobin A1c (HbA1c) and increased frequency of severe hypoglycemia in youth with type 1 diabetes (T1D). Study design International (World Health Organization) and national (Centers for Disease Control and Prevention/German Health Interview and Examination Survey for Children and Adolescents) BMI references were used to calculate BMIz in participants (age 2-<18 years and ≥1 year duration of T1D) enrolled in the T1D Exchange (n = 11 435) and the Diabetes Prospective Follow-up (n = 21 501). Associations between BMIz and HbA1c and severe hypoglycemia were assessed. Results Participants in both registries had median BMI values that were greater than international and their respective national reference values. BMIz was significantly greater in the T1D Exchange vs the Diabetes Prospective Follow-up (P < .001). After stratification by age-group, no differences in BMI between registries existed for children 2-5 years, but differences were confirmed for 6- to 9-, 10- to 13-, and 14- to 17-year age groups (all P < .001). Greater BMIz were significantly related to greater HbA1c levels and more frequent occurrence of severe hypoglycemia across the registries, although these associations may not be clinically relevant. Conclusions Excessive weight is a common problem in children with T1D in Germany and Austria and, especially, in the US. Our data suggest that obesity contributes to the challenges in achieving optimal glycemic control in children and adolescents with T1D

Stimulating at the right time: phase-specific deep brain stimulation.

SEE MOLL AND ENGEL DOI101093/AWW308 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Brain regions dynamically engage and disengage with one another to execute everyday actions from movement to decision making. Pathologies such as Parkinson's disease and tremor emerge when brain regions controlling movement cannot readily decouple, compromising motor function. Here, we propose a novel stimulation strategy that selectively regulates neural synchrony through phase-specific stimulation. We demonstrate for the first time the therapeutic potential of such a stimulation strategy for the treatment of patients with pathological tremor. Symptom suppression is achieved by delivering stimulation to the ventrolateral thalamus, timed according to the patient's tremor rhythm. Sustained locking of deep brain stimulation to a particular phase of tremor afforded clinically significant tremor relief (up to 87% tremor suppression) in selected patients with essential tremor despite delivering less than half the energy of conventional high frequency stimulation. Phase-specific stimulation efficacy depended on the resonant characteristics of the underlying tremor network. Selective regulation of neural synchrony through phase-locked stimulation has the potential to both increase the efficiency of therapy and to minimize stimulation-induced side effects

Nitrogen fixation in the South Atlantic Gyre and the Benguela Upwelling System

Author Posting. © American Geophysical Union, 2011. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 38 (2011): L16608, doi:10.1029/2011GL048315.Dinitrogen (N2) fixation is recognized as an important input of new nitrogen (N) to the open ocean gyres, contributing to the export of organic matter from surface waters. However, very little N2-fixation research has focused on the South Atlantic Gyre, where dust deposition of iron (Fe), an important micronutrient for diazotrophs, is seasonally low. Recent modeling efforts suggest that N2-fixation may in fact be closely coupled to, and greatest in, areas of denitrification, as opposed to the oceanic gyres. One of these areas, the Benguela Upwelling System, lies to the east of the South Atlantic Gyre. In this study we show that N2-fixation in surface waters across the South Atlantic Gyre was low overall (<1.5 nmol N l−1 d−1) with highest rates seen in or near the Benguela Upwelling System (up to ∼8 nmol N l−1 d−1). Surface water dissolved Fe (dFe) concentrations were very low in the gyre (∼0.3 nM or lower), while soluble reactive phosphorus (SRP) concentrations were relatively high (∼0.15 μM). N2-fixation rates across the entire sampling area were significantly positively correlated to dFe, but also to SRP and NO3−. Thus, high NO3− concentrations did not exclude N2-fixation in the upwelling region, which provides evidence that N2-fixation may be occurring in previously unrecognized waters, specifically near denitrification zones. However the gene encoding for a nitrogenase component (nifH) was not detected from known diazotrophs at some stations in or near the upwelling where N2-fixation was greatest, suggesting the presence of unknown diazotrophs in these waters.Funding for this research was provided by NSF grants OCE‐0452883 (to E.A.W. and M.A.S.), OCE‐0825922 (to E.A.W.), and The Gordon and Betty Moore Foundation (JPZ)

Iron availability limits the ocean nitrogen inventory stabilizing feedbacks between marine denitrification and nitrogen fixation

Author Posting. © American Geophysical Union, 2007. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Global Biogeochemical Cycles 21 (2007): GB2001, doi:10.1029/2006GB002762.Recent upward revisions in key sink/source terms for fixed nitrogen (N) in the oceans imply a short residence time and strong negative feedbacks involving denitrification and N fixation to prevent large swings in the ocean N inventory over timescales of a few centuries. We tested the strength of these feedbacks in a global biogeochemical elemental cycling (BEC) ocean model that includes water column denitrification and an explicit N fixing phytoplankton group. In the northern Indian Ocean and over longer timescales in the tropical Atlantic, we find strong stabilizing feedbacks that minimize changes in marine N inventory over timescales of ∼30–200 years. In these regions high atmospheric dust/iron inputs lead to phosphorus limitation of diazotrophs, and thus a tight link between N fixation and surface water N/P ratios. Maintenance of the oxygen minimum zones in these basins depends on N fixation driven export. The stabilizing feedbacks in other regions are significant but weaker owing to iron limitation of the diazotrophs. Thus Fe limitation appears to restrict the ability of N fixation to compensate for changes in denitrification in the current climate, perhaps leading the oceans to lose fixed N. We suggest that iron is the ultimate limiting nutrient leading to nitrogen being the proximate limiting nutrient over wide regions today. Iron stress was at least partially alleviated during more dusty, glacial times, leading to a higher marine N inventory, increased export production, and perhaps widespread phosphorus limitation of the phytoplankton community. The increased efficiency of the biological pump would have contributed to the glacial drawdown in atmospheric CO2.This work was supported by grants from the U.S. National Science Foundation (OCE-0222033 and OCE-0452972). Computations supported by Earth System Modeling Facility (NSF ATM-0321380) and by the Climate Simulation Laboratory at the National Center for Atmospheric Research

Simulating the global distribution of nitrogen isotopes in the ocean

We present a new nitrogen isotope model incorporated into the three-dimensional ocean component of a global Earth system climate model designed for millennial timescale simulations. The model includes prognostic tracers for the two stable nitrogen isotopes, 14N and 15N, in the nitrate (NO3−), phytoplankton, zooplankton, and detritus variables of the marine ecosystem model. The isotope effects of algal NO3− uptake, nitrogen fixation, water column denitrification, and zooplankton excretion are considered as well as the removal of NO3− by sedimentary denitrification. A global database of δ15NO3− observations is compiled from previous studies and compared to the model results on a regional basis where sufficient observations exist. The model is able to qualitatively and quantitatively reproduce many of the observed patterns such as high subsurface values in water column denitrification zones and the meridional and vertical gradients in the Southern Ocean. The observed pronounced subsurface minimum in the Atlantic is underestimated by the model presumably owing to too little simulated nitrogen fixation there. Sensitivity experiments reveal that algal NO3− uptake, nitrogen fixation, and water column denitrification have the strongest effects on the simulated distribution of nitrogen isotopes, whereas the effect from zooplankton excretion is weaker. Both water column and sedimentary denitrification also have important indirect effects on the nitrogen isotope distribution by reducing the fixed nitrogen inventory, which creates an ecological niche for nitrogen fixers and, thus, stimulates additional N2 fixation in the model. Important model deficiencies are identified, and strategies for future improvement and possibilities for model application are outlined

Incorporating a prognostic representation of marine nitrogen fixers into the global ocean biogeochemical model HAMOCC

Nitrogen (N2) fixation is a major source of bioavailable nitrogen to the euphotic zone, thereby exerting an important control on ocean biogeochemical cycling. This paper presents the incorporation of prognostic N2 fixers into the HAMburg Ocean Carbon Cycle model (HAMOCC), a component of the Max Planck Institute Earth System Model (MPI‐ESM). Growth dynamics of N2 fixers in the model are based on physiological characteristics of the cyanobacterium Trichodesmium. The applied temperature dependency confines diazotrophic growth and N2 fixation to the tropical and subtropical ocean roughly between 40°S and 40°N. Simulated large‐scale spatial patterns compare well with observations, and the global N2 fixation rate of 135.6 Tg N yr−1 is within the range of current estimates. The vertical distribution of N2 fixation also matches well the observations, with a major fraction of about 85% occurring in the upper 20 m. The observed seasonal variability at the stations BATS and ALOHA is reasonably reproduced, with highest fixation rates in northern summer/fall. Iron limitation was found to be an important factor in controlling the simulated distribution of N2 fixation, especially in the Pacific Ocean. The new model component considerably improves the representation of present‐day N2 fixation in HAMOCC. It provides the basis for further studies on the role of diazotrophs in global biogeochemical cycles, as well as on the response of N2 fixation to changing environmental conditions